P568: REAL-LIFE EXPERIENCE OF TREATMENT REFRACTORY/RELAPSED ACUTE MYELOID LEUKEMIA PATIENTS WITH VENETOCLAX COMBINATION THERAPY
Authors: H. Pomares Marin, J. Villarreal Hernández, M. Condom Esteve, S. Vives Polo, M. Cervera Calvo, R. Coll Jorda, C. Maluquer Artigal, G. Ibarra Fernández, A. Torrent Catarineu, M. Galiano Barajas, A. M. Sureda Balari, M. Arnan Sangerman
Journal: HemaSphere (2022)

Background: Venetoclax, a BCL-2 specific inhibitor, used in combination with azacitidine in patients with newly-diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy treatment, has shown high response rate and overall survival compared with azacitidine monotherapy (Di Nardo et al. N Engl J Med 2020; 383:617-629). Moreover, Venetoclax in combination with hypomethylating agents or with low-dose cytarabine is being explored in other settings being frequently used in relapsed/refractory (R/R) AML. Aims: We performed a retrospective study of patients with R/R AML receiving venetoclax combinations in the Catalan Institute of Oncology (ICO) in order to determine the efficacy and safety of the combination. Methods: We analyze 60 patients diagnosed with R/R AML at 4 hospitals belonging to ICO in Spain, treated with venetoclax (400mg/24h; initial daily dose of 100mg with a 3-day ramp-up to target dose of 400mg) in combination with hypomethylating agents (Azacitidine 75mg/m2 7/28 days or Decitabine 20mg/m2 5/28 days) or low-dose cytarabine (20mg/m2 10/28 days) from May 2019 until December 2021. Event was defined as death, refractoriness to treatment or progressive disease. Results: Characteristics of our cohort are described in Table 1. Notably, 31 (52%) patients had high-risk AML according to ELN 2017 classification. Fourteen (23%) patients received venetoclax in combination with decitabine, 34 (57%) patients with azacitidine, and 12 (20%) patients with low-dose cytarabine. The median number of cycles received was 3 (range 1-28), with a median of one cycle to achieve the best response (range: 1-4). Early mortality in the first 30 days was 15% (9 patients), 5 due to progression disease, 2 due to infection and 2 due to clinical worsening. Overall response rate after first cycle (Complete response (CR) + complete response without haematological recovery (CRi) + partial response (PR)) was 58%. Three patients were treated in a molecular-MRD positive status, and all of them achieved molecular response. Six of 19 patients (32%) were transitioned to allogeneic stem cell transplantation (alloSCT). The median event-free survival and overall survival was 5.03 months and 7.2 months, respectively. Response to treatment after 3-4 cycles, discriminate two groups of patients with an OS of 12.66 months in those patients who achieved CR or PR vs 2.4 months in non-responders (p0.000). Patients relapsed after alloSCT (7 patients) presented a poor outcome (median OS was 1.6 months). Image:Summary/Conclusion: Our study showed that real-world experience of treating patients with R/R AML with venetoclax in combination with hypomethylating agents or low-dose cytarabine is feasible as salvage treatment in patients relapsed to hypomethylating agent and as bridge therapy to alloSCT with a rapid response rate. Moreover, rapid responses shown with the combination, allow us to identificate those patients who may benefit from this approach.